New ternary Fe(III)-8-hydroxyquinoline–reduced Schiff base complexes as selective anticancer drug candidates

FERRETTI, VALERIA; MATOS, CRISTINA P.; CANELAS, CATARINA; PESSOA, JOÃO COSTA; TOMAZ, ANA ISABEL; STAROSTA, RADOS?AW; CORREIA, ISABEL; LEÓN, IGNACIO E.

JOURNAL OF INORGANIC BIOCHEMISTRY

ELSEVIER SCIENCE INC

Año: 2022 vol. 236

0162-0134

Due to the growing prevalence of cancer diseases, new therapeutic options are urgently needed, and drugs basedon metal ions other than platinum are alternatives with exciting possibilities. We report the synthesis, characterizationandbiologicaleffectofmixed-ligandFe(III)-aminophenolatecomplexesderivedfromsalicylaldehydeandL-tryptophan with quinoline derivatives as co-ligands, namely 8-hydroxyquinoline (8HQ), [Fe(L)(8HQ)(H2O)] (1) and its 5-cloro derivative (Cl8HQ), [Fe(L)(Cl8HQ)(HO)] (2). The complex bearing the aminophenolateand lacking the quinoline co-ligand, [Fe(L)(Cl)(H2O)2] (3), was prepared for comparison. Theanalytical and spectroscopic characterization revealed that 1 and 2 are octahedral Fe(III) complexes with theaminophenolate acting as a dianionic tridentate ligand and 8HQ co-ligands as bidentate chelates. Spectroscopictechniques and molecular docking studies were used to evaluate the ability of these complexes to bind bovineserum albumin (BSA) and calf thymus DNA. Complex 2 [Fe(L)(Cl8HQ)(H2O)] was the one showing higher affinityfor both biomolecules. Cell viability was assessed in breast, colorectal and bone human cancer cell lines. 1 and 2were found to be more active than cisplatin in all cell lines tested. A non-tumoral fibroblast line (L929, mousenon-tumoral fibroblasts) was used to evaluate selectivity. The results evidence that 2 shows much higherselectivity than 1 in all cell lines tested, but particularly in bone cancer cells in which selectivity index (SI) valuesare 8.0 and 18.8 for 1 and 2, respectively. 2